[Laboratory test values in children significantly depend on age: focus on alkaline phosphatase (ALP), alpha-fetoprotein (AFP), and immunoglobulins].
Laboratory test reference values are collected from a group of individuals presumed to be healthy to serve as controls in diagnostic comparisons. Pediatric test reference values sometimes vary from those of adults and/or among children of different ages based on their development and growth. Therefore, it is crucial to obtain age-matched laboratory test reference values. As the acquisition of samples from healthy children has become extremely difficult in recent years, clinical reference ranges calculated from routine laboratory data of patients using a statistical method have been used in some institutions, including our own. In addition, clinical judgment has become increasingly important for interpreting laboratory tests that are relatively less common and/or show marked variation. This article reviews pediatric laboratory test values of markers that are variable at different ages, such as alkaline phosphatase (ALP), alpha-fetoprotein (AFP), and immunoglobulins. In general, the serum level of ALP in a pediatric population is two to three times higher than that of an adult population. Circulating AFP levels are markedly higher in neonates just after birth and then decrease exponentially, reaching close to the average adult value by late infancy. Immunoglobulins, except for IgG, increase after birth in infancy. In contrast, IgG levels drop in early infancy due to the reduction of maternal IgG, and then rise as a result of increased IgG production. As these laboratory test values significantly depend on the age, they should be used with caution. Furthermore, it is deemed desirable to apply newly developed laboratory tests that have been shown to be beneficial in adults to a pediatric clinical setting.


Electrical impedance scanning of lymph nodes: initial clinical and technical findings.
The sonographic differentiation between inflammatory and malignant lymph node enlargement remains imprecise. Electrical impedance scanning (EIS) is of more value in malignant breast lesions, and this study was undertaken to determine if it was of use in differentiating nodal enlargement. Two hundred and thirty-six sonographically suspicious lymph nodes (146 patients) of mean size 18 x 11 x 11 mm mean depth 9 mm were examined using a commercially available electrical impedance imaging system. The following locations of lymph nodes were included in the study: cervical, axillary, inguinal, supraclavicular and chest/abdominal wall. The EIS results were compared to histopathological, serological or follow up findings. Using EIS 105/115 malignant nodes were correctly diagnosed, while 70/121 inflammatory or benign lymph nodes were correctly identified as benign by EIS (10 false-negative, 51 false-positive). Sensitivity (91.3%) and specificity (57.9%) were obtained. Corresponding negative and positive predictive values were 87.5% and 67.3%, respectively. Results from this initial study suggest potential value for EIS as an imaging adjunct in the differentiation of sonographically equivocal lesions. Best accuracy was achieved at chest/abdominal wall and inguinal locations. Due to technical restrictions with the present system, the examination of inframandibular and para-aortal lymph nodes should be limited to special cases.


Vaccinia virus and Cowpox virus are not susceptible to the interferon-induced antiviral protein MxA.
MxA protein is expressed in response to type I and type III Interferon and constitute an important antiviral factor with broad antiviral activity to diverse RNA viruses. In addition, some studies expand the range of MxA antiviral activity to include particular DNA viruses like Monkeypox virus (MPXV) and African Swine Fever virus (ASFV). However, a broad profile of activity of MxA to large DNA viruses has not been established to date. Here, we investigated if some well characterized DNA viruses belonging to the Poxviridae family are sensitive to human MxA. A cell line inducibly expressing MxA to inhibitory levels showed no anti-Vaccinia virus (VACV) virus activity, indicating either lack of susceptibility of the virus, or the existence of viral factors capable of counteracting MxA inhibition. To determine if VACV resistance to MxA was due to a virus-encoded anti-MxA activity, we performed coinfections of VACV and the MxA-sensitive Vesicular Stomatitis virus (VSV), and show that VACV does not protect VSV from MxA inhibition in trans. Those results were extended to several VACV strains and two CPXV strains, thus confirming that those Orthopoxviruses do not block MxA action. Overall, these results point to a lack of susceptibility of the Poxviridae to MxA antiviral activity.


Composition dependent mechanical behaviour of S53P4 bioactive glass putty for bone defect grafting.
To improve the handling properties of S53P4 bioactive glass granules for clinical applications, bioactive glass putty formulations were developed. These formulations contain both granules and a synthetic binder to form an injectable material that is easy to shape. To explore its applicability in load-bearing bone defect grafting, the relation between the putty composition and its mechanical behaviour was assessed in this study. Five putty formulations with variations in synthetic binder and granule content were mechanically tested in confined compression. The results showed that the impaction strains significantly decreased and the residual strains significantly increased with an increasing binder content. The stiffness of all tested formulations was found to be in the same range as the reported stiffness of cancellous bone. The measured creep strains were low and no significant differences between formulations were observed. The stiffness significantly increased when the samples were subjected to a second loading stage. The residual strains calculated from this second loading stage were also significantly different from the first loading stage, showing an increasing difference with an increasing binder content. Since residual strains are detrimental for graft layer stability in load-bearing defects, putty compositions with a low binder content would be most beneficial for confined, load-bearing bone defect grafting.


Statin therapy, fitness, and mortality risk in middle-aged hypertensive male veterans.
Hypertension often coexists with dyslipidemia, accentuating cardiovascular risk. Statins are often prescribed in hypertensive individuals to lower cardiovascular risk. Higher fitness is associated with lower mortality, but exercise capacity may be attenuated in hypertension. The combined effects of fitness and statin therapy in hypertensive individuals have not been assessed. Thus, we assessed the combined health benefits of fitness and statin therapy in hypertensive male subjects. Peak exercise capacity was assessed in 10,202 hypertensive male subjects (mean age = 60.4 ± 10.6 years) in 2 Veterans Affairs Medical Centers. We established 4 fitness categories based on peak metabolic equivalents (METs) achieved and 8 categories based on fitness status and statin therapy. During the follow-up period (median = 10.2 years), there were 2,991 deaths. Mortality risk was 34% lower (hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.59-0.74; P < 0.001) among individuals treated with statins compared with those not on statins. The fitness-related mortality risk association was inverse and graded regardless of statin therapy status. Risk reduction associated with exercise capacity of 5.1-8.4 METs was similar to that observed with statin therapy. However, those achieving ≥8.5 METs had 52% lower risk (HR = 0.48; 95% CI = 0.37-0.63) when compared with the least-fit subjects (≤5 METs) on statin therapy. The combination of statin therapy and higher fitness lowered mortality risk in hypertensive individuals more effectively than either alone. The risk reduction associated with moderate increases in fitness was similar to that achieved by statin therapy. Higher fitness was associated with 52% lower mortality risk when compared with the least fit subjects on statin therapy.


A correlation of endocrine and anticancer effects of some antagonists of GHRH.
GHRH receptor antagonists inhibit growth and metastasis of a large number of experimental tumors expressing the pituitary GHRH receptor (pGHRH-R) and its major splice variant SV1. In this study, using Western blot, we demonstrated that DBTRG-05 and U-87MG human glioblastoma cell lines express pGHRH-R at levels 6-15 times higher than SV1. To reveal a correlation between the anticancer activity and the endocrine potency on inhibition of GH release, we compared the antitumor effect of GHRH antagonists JV-1-63 and MZJ-7-138 on growth of DBTRG-05 human glioblastomas grafted into athymic nude mice with their inhibitory potency on GH release. JV-1-63 strongly suppressed the stimulated GH secretion induced by clonidine in rats and inhibited the exogenous GHRH-induced GH surge by 88-99% in vivo and in vitro. MZJ-7-138 decreased the stimulated GH secretion by 58% in vitro and showed only a tendency to inhibit GH secretion in vivo. The strong inhibitor of GH release JV-1-63 reduced tumor growth of DBTRG-05 glioblastomas in nude mice by 46%, while the weak GH release suppressor MZJ-7-138 did not have an effect. Exposure of DBTRG-05 cells to the GHRH antagonists in vitro caused an upregulation of mRNA expression for pGHRH-R and a downregulation of SV1 expression, with JV-1-63 having significantly greater effects than MZJ-7-138. Our results demonstrate that a positive correlation exists between the endocrine potency and the antiproliferative efficacy of GHRH antagonists in tumors strongly expressing pGHRH-R.


Upregulation of valosin-containing protein (VCP) is associated with poor prognosis and promotes tumor progression of orbital B-cell lymphoma.
This study aimed to investigate the relationship between VCP expression and the prognosis of orbital B-cell lymphoma patients and the influence of downregulation of VCP on the apoptosis and invasion abilities of lymphoma cells. We recruited 66 orbital B-cell lymphoma patients. VCP expression in 66 samples of orbital B-cell lymphoma was determined by immunohistochemistry using monoclonal VCP antibodies. Based on VCP-expression levels detected by immunohistochemistry, we chose ten cases of orbital tumor paraffin tissue from the patients. Total RNA was extracted and differences in VCP gene-expression levels compared among patients using quantitative reverse-transcription (qRT) PCR. We used siRNA to knock down VCP in the lymphoma cell lines Raji and SUDHL4. qRT-PCR and Western blot were applied to detect VCP mRNA and protein expression, respectively. SUDHL48 assays were applied to investigate cell proliferation. Hoechst 33258 staining and flow-cytometry analysis were applied to investigate cell apoptosis. Transwell assays were applied to investigate invasive ability. Survival analysis was used to evaluate prognostic values. Expression levels of VCP were correlated with the stage, tumor grade, and recurrence rate of patients. VCP mRNA-expression levels were consistent with VCP-expression levels in orbital B-cell lymphoma tissue. Moreover, survival analysis revealed that lower VCP-expression levels were correlated with longer overall survival of orbital B-cell lymphoma patients. Down-regulation of VCP with siRNA did not inhibit cell proliferation. However, it dramatically increased apoptosis and suppressed the invasion of B-cell lymphoma cells. VCP expression played an important role in the progression of orbital B-cell lymphoma. VCP could be a useful marker for predicting the prognosis of orbital B-cell lymphoma patients. VCP may be a potential therapeutic target for orbital B-cell lymphoma.


Predicting Kidney Graft Survival Using Machine Learning Methods: Prediction Model Development and Feature Significance Analysis Study.
Kidney transplantation is the optimal treatment for patients with end-stage renal disease. Short- and long-term kidney graft survival is influenced by a number of donor and recipient factors. Predicting the success of kidney transplantation is important for optimizing kidney allocation. The aim of this study was to predict the risk of kidney graft failure across three temporal cohorts (within 1 year, within 5 years, and after 5 years following a transplant) based on donor and recipient characteristics. We analyzed a large data set comprising over 50,000 kidney transplants covering an approximate 20-year period. We applied machine learning-based classification algorithms to develop prediction models for the risk of graft failure for three different temporal cohorts. Deep learning-based autoencoders were applied for data dimensionality reduction, which improved the prediction performance. The influence of features on graft survival for each cohort was studied by investigating a new nonoverlapping patient stratification approach. Our models predicted graft survival with area under the curve scores of 82% within 1 year, 69% within 5 years, and 81% within 17 years. The feature importance analysis elucidated the varying influence of clinical features on graft survival across the three different temporal cohorts. In this study, we applied machine learning to develop risk prediction models for graft failure that demonstrated a high level of prediction performance. Acknowledging that these models performed better than those reported in the literature for existing risk prediction tools, future studies will focus on how best to incorporate these prediction models into clinical care algorithms to optimize the long-term health of kidney recipients.


PTEN limits alveolar macrophage function against Pseudomonas aeruginosa after bone marrow transplantation.
Hematopoietic stem cell transplant patients are susceptible to infection despite cellular reconstitution. In a murine model of syngeneic bone marrow transplantation (BMT), we previously reported that BMT mice have impaired host defense against Pseudomonas aeruginosa pneumonia due to overproduction of (PG)E(2) in lung. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an effector in the PGE(2) signaling pathway that negatively regulates alveolar macrophage (AM) phagocytosis and bacterial killing. Therefore, examined whether overproduction of PGE(2) after BMT inhibits AM host defense by up-regulating PTEN phosphatase activity. We found that PTEN activity is elevated in BMT AMs in response to increased PGE(2) signaling and that pharmacological inhibition of PTEN activity in BMT AMs fully restores phagocytosis of serum-opsonized P. aeruginosa but only partially restores phagocytosis of nonopsonized P. aeruginosa. In wild-type mice transplanted with myeloid-specific conditional PTEN knockout (PTEN CKO) bone marrow, bacterial clearance is improved after challenge with P. aeruginosa pneumonia. Furthermore, PTEN CKO BMT AMs display improved TNF-α production and enhanced phagocytosis and killing of serum-opsonized P. aeruginosa despite overproduction of PGE(2). However, AM phagocytosis of nonopsonized P. aeruginosa is only partially restored in the absence of PTEN after BMT. This may be related to elevated AM expression of IL-1 receptor-associated kinase (IRAK)-M, a molecule previously identified in the PGE(2) signaling pathway to inhibit AM phagocytosis of nonopsonized bacteria. These data suggest that PGE(2) signaling up-regulates IRAK-M independently of PTEN and that these molecules differentially inhibit opsonized and nonopsonized phagocytosis of P. aeruginosa.


Orthodontic treatment in children with cleft lip and palate repaired using a two-stage surgical correction - authors' experience.
The purpose of this study was to present and evaluate orthodontic rules and methods in the treatment of children and adolescents with complete cleft lip and palate. The material consists of about 5500 primary clefts treated at the Hospital and Clinic of Plastic Surgery in Polanica-Zdrój in the years 1976-2008. The most common surgical procedure (>99%) consisted of two-stage repair of cleft lip and palate. In the years 1976-2008, surgical treatment was administered to 5,500 children with a cleft lip and palate. The efficiency of orthodontic procedures is discussed in relation to multidisciplinary cooperation, with a particular emphasis on surgery. Apart from cleft morphology and the quality of primary surgery, the patients appearance, midface development and occlusal conditions depend on multidisciplinary cooperation, with special regard given to orthodontic treatment.


Effect of Thoracic Epidural Anesthesia on Ventricular Excitability in a Porcine Model.
Imbalances in the autonomic nervous system, namely, excessive sympathoexcitation, contribute to ventricular tachyarrhythmias. While thoracic epidural anesthesia clinically suppresses ventricular tachyarrhythmias, its effects on global and regional ventricular electrophysiology and electrical wave stability have not been fully characterized. The authors hypothesized that thoracic epidural anesthesia attenuates myocardial excitability and the proarrhythmic effects of sympathetic hyperactivity. Yorkshire pigs (n = 15) had an epidural catheter inserted (T1 to T4) and a 56-electrode sock placed on the heart. Myocardial excitability was measured by activation recovery interval, dispersion of repolarization, and action potential duration restitution at baseline and during programed ventricular extrastimulation or left stellate ganglion stimulation, before and 30 min after thoracic epidural anesthesia (0.25% bupivacaine). After thoracic epidural anesthesia infusion, there was no change in baseline activation recovery interval or dispersion of repolarization. During programmed ventricular extrastimulation, thoracic epidural anesthesia decreased the maximum slope of ventricular electrical restitution (0.70 ± 0.24 vs. 0.89 ± 0.24; P = 0.021) reflecting improved electrical wave stability. Thoracic epidural anesthesia also reduced myocardial excitability during left stellate ganglion stimulation-induced sympathoexcitation through attenuated shortening of activation recovery interval (-7 ± 4% vs. -4 ± 3%; P = 0.001), suppression of the increase in dispersion of repolarization (313 ± 293% vs. 185 ± 234%; P = 0.029), and reduction in sympathovagal imbalance as measured by heart rate variability. Our study describes the electrophysiologic mechanisms underlying antiarrhythmic effects of thoracic epidural anesthesia during sympathetic hyperactivity. Thoracic epidural anesthesia attenuates ventricular myocardial excitability and induces electrical wave stability through its effects on activation recovery interval, dispersion of repolarization, and the action potential duration restitution slope.


Supplementation of ammoniated wheat straw: performance and forage utilization characteristics in beef cattle receiving energy and protein supplements.
Two experiments were conducted to evaluate performance and forage utilization characteristics of beef cattle fed ammoniated wheat straw (AWS) unsupplemented except for minerals or supplemented with energy and protein. In Exp. 1, 194 crossbred beef cows (BW = 472 kg) in late gestation were allotted by weight, breed type, and age during two consecutive winters to 12 drylot pens (three pens/treatment) for a 60-d feeding trial. The AWS (3% NH3 wt/wt) was tubground through a 7.6-cm screen, and cows were allowed ad libitum access to the AWS. In Exp. 2, 16 ruminally fistulated Angus x Hereford steers (BW = 300 kg) were blocked by weight and randomized to treatments in a 35-d intake-digestion trial. Daily supplementation treatments in both experiments were Control, no supplemental energy or protein; LSG, 1.36 kg of sorghum grain (SG); HSG, 2.72 kg of SG; and SG + SBM, 1.02 kg of SG + .34 kg of soybean meal (SBM). All animals received .23 kg of mineral mixture formulated to meet a pregnant cow's mineral requirements. Supplements LSG and SG + SBM were fed to provide the same daily ME, and HSG and SG + SBM were fed to provide the same daily CP. Cows were managed as one group during and after calving. In Exp. 1, all supplements increased gain (P less than .01) vs Control, and cows fed SG + SBM had higher (P = .05) gains than those fed LSG. The SG + SBM supplement increased (P less than .01) change in cow body condition score compared with LSG.(ABSTRACT TRUNCATED AT 250 WORDS)


The microRNA miR-8 is a positive regulator of pigmentation and eclosion in Drosophila.
MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally silence gene expression by binding to target mRNAs. Previous studies have identified the miRNA miR-8 as a pleiotropic regulator of Drosophila development, controlling body size and neuronal survival by targeting multiple mRNAs. In this study we demonstrate that miR-8 is also required for proper spatial patterning of pigment on the adult abdominal cuticle in females but not males. Female adult flies lacking miR-8 exhibit decreased pigmentation of the dorsal abdomen, with a pattern of pigmentation similar to wild type flies grown at higher temperatures. This pigmentation defect in miR-8 mutants is independent of the previously reported body size defect, and miR-8 acts directly in the developing cuticle to regulate pigmentation patterning. The decrease in pigmentation in miR-8 mutants was more pronounced in flies grown at higher temperatures. We also found that loss of miR-8 dramatically affected the ability to eclose at higher temperatures. Loss of miR-8 increased the sensitivity of Drosophila to higher temperatures for both pigmentation patterning and the ability to eclose. Together, these data suggest that miR-8 acts as a buffer to stabilize gene expression patterns in the midst of environmental variation.


Assessing the quality of teleconsultations in a store-and-forward telemedicine network.
Store-and-forward telemedicine in resource-limited settings is becoming a relatively mature activity. However, there are few published reports about quality measurement in telemedicine, except in image-based specialties, and they mainly relate to high- and middle-income countries. In 2010, Médecins Sans Frontières (MSF) began to use a store-and-forward telemedicine network to assist its field staff in obtaining specialist advice. To date, more than 1000 cases have been managed with the support of telemedicine, from a total of 40 different countries. We propose a method for assessing the overall quality of the teleconsultations provided in a store-and-forward telemedicine network. The assessment is performed at regular intervals by a panel of observers, who - independently - respond to a questionnaire relating to a randomly chosen past case. The answers to the questionnaire allow two different dimensions of quality to be assessed: the quality of the process itself and the outcome, defined as the value of the response to three of the four parties concerned, i.e., the patient, the referring doctor, and the organization. It is not practicable to estimate the value to society by this technique. The feasibility of the method was demonstrated by using it in the MSF telemedicine network, where process quality scores, and user-value scores, appeared to be stable over a 9-month trial period. This was confirmed by plotting the cusum of a portmanteau statistic (the sum of the four scores) over the study period. The proposed quality-assessment method appears feasible in practice, and will form one element of a quality assurance program for MSF's telemedicine network in future. The method is a generally applicable one, which can be used in many forms of medical interaction.


Explainable Depression Detection Based on Facial Expression Using LSTM on Attentional Intermediate Feature Fusion with Label Smoothing.
Machine learning is used for a fast pre-diagnosis approach to prevent the effects of Major Depressive Disorder (MDD). The objective of this research is to detect depression using a set of important facial features extracted from interview video, e.g., radians, gaze at angles, action unit intensity, etc. The model is based on LSTM with an attention mechanism. It aims to combine those features using the intermediate fusion approach. The label smoothing was presented to further improve the model's performance. Unlike other black-box models, the integrated gradient was presented as the model explanation to show important features of each patient. The experiment was conducted on 474 video samples collected at Chulalongkorn University. The data set was divided into 134 depressed and 340 non-depressed categories. The results showed that our model is the winner, with a 88.89% F1-score, 87.03% recall, 91.67% accuracy, and 91.40% precision. Moreover, the model can capture important features of depression, including head turning, no specific gaze, slow eye movement, no smiles, frowning, grumbling, and scowling, which express a lack of concentration, social disinterest, and negative feelings that are consistent with the assumptions in the depressive theories.


Stem-pitting caused by Citrus tristeza virus is associated with increased phloem occlusion.
Stem-pitting (SP) disease results from disruption of normal phloem and xylem development. In citrus, a characteristic manifestation of SP caused by Citrus tristeza virus (CTV) is phloem regeneration. We hypothesized that phloem regeneration occurs due to reduced functionality of CTV infected phloem cells. To examine phloem cell occlusions in CTV-SP, we analyzed callose and phloem-protein (PP) accumulation in Citrus macrophylla trees infected with CTV mutants exhibiting different SP phenotypes from very mild (CTVΔp13) to severe (CTVΔp33), in addition to full-length CTV and healthy plants. CTV infection was accompanied by callose and PP accumulation in the phloem. With the increase in the SP symptoms from very mild to severe, there was a constant increase in the levels of callose and PP, accompanied by an increase in PHLOEM-PROTEIN 2 and a decrease in BETA-1,3-GLUCANASE gene expression levels. These results indicate that SP symptom development is associated with increased phloem occlusion.


Nitrogen assimilation in alfalfa: isolation and characterization of an asparagine synthetase gene showing enhanced expression in root nodules and dark-adapted leaves.
Asparagine, the primary assimilation product from N2 fixation in temperate legumes and the predominant nitrogen transport product in many plant species, is synthesized via asparagine synthetase (AS; EC 126.96.36.199). Here, we report the isolation and characterization of a cDNA and a gene encoding the nodule-enhanced form of AS from alfalfa. The AS gene is comprised of 13 exons separated by 12 introns. The 5' flanking region of the AS gene confers nodule-enhanced reporter gene activity in transformed alfalfa. This region also confers enhanced reporter gene activity in dark-treated leaves. These results indicate that the 5' upstream region of the AS gene contains elements that affect expression in root nodules and leaves. Both AS mRNA and enzyme activity increased approximately 10- to 20-fold during the development of effective nodules. Ineffective nodules have strikingly reduced amounts of AS transcript. Alfalfa leaves have quite low levels of AS mRNA and protein; however, exposure to darkness resulted in a considerable increase in both. In situ hybridization with effective nodules and beta-glucuronidase staining of nodules from transgenic plants showed that AS is expressed in both infected and uninfected cells of the nodule symbiotic zone and in the nodule parenchyma. RNA gel blot analysis and in situ hybridization results are consistent with the hypothesis that initial AS expression in nodules is independent of nitrogenase activity.


The speech pathology treatment with alterations of the stomatognathic system.
This article analyzes differences in orthodontic and craniofacial classifications and the role of the speech-language pathologist in adequately treating those patients with varying Class II and Class III malocclusions. Other symptoms, such as those of mouth breathing and tongue position, are compared and contrasted in order to identify characteristics and treatment issues pertaining to each area. The author emphasizes a team approach to myofunctional therapy and stresses the importance of collaborative treatment.


The Relationship Between Course of Illness and β-Endorphin Plasma Levels in Patients with Schizophrenia.
Extensive investigations have been conducted into predictors of schizophrenia outcome. The heterogeneity of the illness implies that many factors should be taken into account. Some studies have reported the relationship between increased β-endorphin concentration and predominant negative symptoms. We included 77 outpatients with schizophrenia and 74 healthy controls. Data referring to duration and course of illness, hospitalization number and treatment were collected on the basis of clinical interviews and medical documentation analysis. The β-endorphin concentrations were assessed once in all participants, at the onset of the study. A chronic course of illness was found in 44 of the 77 schizophrenics. Patients with schizophrenia, especially those with a chronic course of illness, revealed significantly higher β-endorphin concentrations than those with an episodic course and controls (mean 29.70 vs 19.86 pmol/L; p=0.0001). Increased levels of β-endorphin were related to longer duration of illness (R=0.294, p=0.009) and frequent psychiatric hospitalization (R=0.346, p=-0.002). Endorphins may be potential biological predictors of persistent negative symptoms and final outcome in schizophrenia.


Examining the effects of self-assembled monolayers on nanoporous gold based amperometric glucose biosensors.
Nanoporous gold (NPG) based biosensors have been constructed by covalently immobilizing glucose oxidase (GOx) onto self-assembled monolayers (SAMs). With p-benzoquinone (BQ) as a mediator, diffusion behavior and amperometric biosensor performance are evaluated by electrochemical characterization. The enzyme modified electrodes are demonstrated to show a thickness-sensitive behavior. Compared with planar polycrystalline gold, the unique porous structure of NPG has also been characterized via an electrochemical surface reconstruction process. Single-crystal gold-like electrochemical behavior on NPG and a comprehensive understanding of its impacts on sensor performance have been proposed.


Recovery potential of the world's coral reef fishes.
Continuing degradation of coral reef ecosystems has generated substantial interest in how management can support reef resilience. Fishing is the primary source of diminished reef function globally, leading to widespread calls for additional marine reserves to recover fish biomass and restore key ecosystem functions. Yet there are no established baselines for determining when these conservation objectives have been met or whether alternative management strategies provide similar ecosystem benefits. Here we establish empirical conservation benchmarks and fish biomass recovery timelines against which coral reefs can be assessed and managed by studying the recovery potential of more than 800 coral reefs along an exploitation gradient. We show that resident reef fish biomass in the absence of fishing (B0) averages ∼1,000 kg ha(-1), and that the vast majority (83%) of fished reefs are missing more than half their expected biomass, with severe consequences for key ecosystem functions such as predation. Given protection from fishing, reef fish biomass has the potential to recover within 35 years on average and less than 60 years when heavily depleted. Notably, alternative fisheries restrictions are largely (64%) successful at maintaining biomass above 50% of B0, sustaining key functions such as herbivory. Our results demonstrate that crucial ecosystem functions can be maintained through a range of fisheries restrictions, allowing coral reef managers to develop recovery plans that meet conservation and livelihood objectives in areas where marine reserves are not socially or politically feasible solutions.


Prevalence and extent of mitral annular disjunction in structurally normal hearts: comprehensive 3D analysis using cardiac computed tomography.
Mitral annular disjunction is fibrous separation between the attachment of the posterior mitral leaflet and the basal left ventricular myocardium initially described in dissected hearts. Currently, it is commonly evaluated by echocardiography, and potential relationships with mitral valve prolapse and ventricular arrhythmia have been suggested. However, controversy remains as its prevalence and extent have not been fully elucidated in normal living subjects. Systolic datasets of cardiac computed tomography obtained from 98 patients (mean age, 69.1 ± 12.6 years; 81% men) with structurally normal hearts were assessed retrospectively. Circumferential extent of both mitral leaflets and disjunction was determined by rotating orthogonal multiplanar reconstruction images around the central axis of the mitral valvar orifice. Distribution angle within the circumference of the mitral valvar attachment and maximal height of disjunction were quantified. In total, 96.0% of patients demonstrated disjunction. Average distribution angles of the anterior and posterior mitral leaflets were 91.3 ± 9.4° and 269.8 ± 9.7°, respectively. Average distribution angle of the disjunction was 105.1 ± 49.2°, corresponding to 39.0 ± 18.2% of the entire posterior mitral valvar attachment. Median value of the maximal height of disjunction was 3.0 (1.5-7.0) mm. Distribution prevalence map of the disjunction revealed characteristic double peaks, with frequent sites of the disjunction located at the anterior to antero-lateral and inferior to infero-septal regions. Mitral annular disjunction is a rather common finding in the normal adult heart with bimodal distribution predominantly observed involving the P1 and P3 scallops of the posterior mitral leaflet.


Effects of tegaserod and erythromycin in upper gut dysmotility: a comparative study.
Tegaserod may enhance upper gut transit, but, its prokinetic effects on antral/small bowel motility and how this compares with erythromycin is unknown. We prospectively assessed and compared the effects of tegaserod and erythromycin on upper gut motility. In an open label, non-crossover study, 22 patients (M/F=4/18; mean age=37 years) with symptoms of upper gut dysmotility underwent 24-hour ambulatory antroduodenojejunal manometry with a six-sensor solid state probe. The effects of 12 mg oral tegaserod were compared with 125 mg intravenous erythromycin by quantifying pressure wave activity and assessing motor patterns. Motor activity increased (p<0.05) in antrum, duodenum and jejunum with both drugs when compared to baseline period. The motor response with tegaserod was higher (p<0.05) in jejunum and occurred during the second or third hours, whereas with erythromycin, it was higher (p<0.05) in antrum and occurred within 30 minutes. After tegaserod, a 'fed-response' like pattern was seen whereas after erythromycin, large amplitude (>100 mmHg) antral contractions at 3 cycles per minute were seen. Following tegaserod and erythromycin, phase III MMCs occurred in 12 (55%) and 8 (36%) patients respectively (p>0.05). Both drugs increase upper gut motility and induce MMC's, but exert a differential response. Tegaserod produces a more sustained prokinetic effect in the duodenum/jejunum, whereas erythromycin predominantly increases antral motor activity.


Pathophysiology and treatment of typical and atypical hemolytic uremic syndrome.
Hemolytic uremic syndrome is a rare disease, frequently responsible for renal insufficiency in children. Recent findings have led to renewed interest in this pathology. The discovery of new gene mutations in the atypical form of HUS and the experimental data suggesting the involvement of the complement pathway in the typical form, open new perspectives for treatment. This review summarizes the current state of knowledge on both typical and atypical hemolytic uremic syndrome pathophysiology and examines new perspectives for treatment.


Prevalence of ADHD and comorbid disorders among elementary school children screened for disruptive behavior.
In the context of a school-based prevention of conduct disorder program, 7,231 first- through fourth-grade children were screened for cross-setting disruptive behavior. Frequencies of DSM-III-R psychiatric disorders and patterns of comorbidity were assessed. We also examined the association of psychiatric diagnosis with child and parent characteristics to determine differential risk based on diagnostic subgroups. Attention deficit hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD) were the most frequent diagnoses. Mood and anxiety disorders were infrequent as single diagnoses. Patterns of comorbidity demonstrated that both externalizing and internalizing disorders commonly cooccurred with ADHD. More severe degrees of psychopathology and psychosocial risk accrued to the subgroup of youths with ADHD plus a comorbid externalizing disorder.


[Current problems of medical microbiology: Achievements, tasks and perspectives].
Two important problems of current medical microbiology are discussed in this paper: 1) a change of etiological structure of infectious morbidity-elevation of the incidence of infections caused by conditioned pathogenic causative agents, and 2) postvaccinal complications. In the light of these problems the tasks of microbiological investigations for the immediate future are discussed. Tasks and prospects of study of the molecular structure of the pathogenicity factors of importance for the creation of chemical vaccines and genetic investigations which would provide construction of strains and preparations useful in practice are formulated.


Chloroquine for influenza prevention: a randomised, double-blind, placebo controlled trial.
Chloroquine has in-vitro activity against influenza and could be an ideal candidate for worldwide prevention of influenza in the period between onset of a pandemic with a virulent influenza strain and the development and widespread dissemination of an effective vaccine. We aimed to assess the efficacy of such an intervention. In this randomised, double-blind, placebo-controlled trial done at a single centre in Singapore, we randomly assigned (1:1) healthy adults to receive chloroquine phosphate (500 mg/day for 1 week, then once a week to complete 12 weeks) or matching placebo by use of a computer-generated randomisation list. Participants filled an online symptom diary every week, supplemented by daily diaries and self-administered nasal swabs when unwell. Haemagglutination-inhibition assays for influenza A (H1N1, H3N2) and B were done on blood samples taken at baseline and after 12 weeks. The primary outcome was laboratory-confirmed clinical influenza defined by specific symptoms accompanied by influenza RNA on nasal swabs or a four-fold increase in haemagglutination-inhibition titres over the 12-week study period. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT01078779. From November, 2009, to February, 2010, we recruited 1516 eligible participants. 1496 (96%) returned at week 12 and were included in the efficacy analysis. Adherence to study intervention was 97%, and 94% of the scheduled weekly diaries were completed. Eight (1%) of 738 participants had laboratory-confirmed clinical influenza in the placebo group and 12 (2%) of 724 in the chloroquine group (relative risk 1·53, 95% CI 0·63-3·72; p=0·376). 29 (4%) of 738 had laboratory-confirmed influenza infection (symptomatic or asymptomatic) in the placebo group and 38 (5%) of 724 in the chloroquine group (1·34, 0·83-2·14; p=0·261). 249 (33%) of 759 participants reported adverse events (mostly mild) in the placebo group and 341 (45%) of 757 in chloroquine group (p<0·0001). Headache, dizziness, nausea, diarrhoea, and blurred vision were more common in the chloroquine group, but rarely resulted in treatment discontinuation. One serious adverse event (hepatitis) was possibly related to chloroquine. Although generally well tolerated by a healthy community population, chloroquine does not prevent infection with influenza. Alternative drugs are needed for large-scale prevention of influenza. National Medical Research Council, Singapore.


Atypical patterns of neural infection produced in mice by drug-resistant strains of herpes simplex virus.
Mice inoculated intracerebrally (i.c.) with a mutant strain of HSV were found to develop cataracts 1 to 2 months after inoculation. Cataract formation was subsequently shown to follow an acute retinitis which commenced within 1 week of inoculation. The mutant had been selected for high resistance to the nucleoside analogue acyclovir and has been shown previously to be defective in the induction of thymidine kinase and also to express an altered DNA polymerase. The LD50 for mice inoculated i.c. was greater than 10(5) p.f.u. compared with approx 7 p.f.u. for the parental strain. Studies of virus replication following i.c. inoculation with a sublethal dose of the mutant revealed that only small amounts of infectious virus were produced in the brain, but during a period from 6 to 12 days after inoculation vigorous replication occurred in retinal tissue, producing very high titres of virus.


Biophysical analysis of cancer stem cell-potent copper(ii) coordination complexes.
Copper(ii) coordination complexes, 1 and 2, containing nonsteroidal anti-inflammatory drugs (NSAIDs) potently kill breast cancer stem cells (CSCs) and bulk breast cancer cells. Although detailed biological studies have been conducted to shed light on their mechanism of cytotoxicity, little is known about their molecular level mechanism of action. This biophysical study, aided by the preparation of a fluorophore-containing analogue, 3, reveals that the complexes operate by undergoing reduction to a copper(i) form and releasing the associated NSAIDs.


Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism.
Congenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A) are known to cause CHI. To characterise the clinical and molecular aspects of a large cohort of patients with CHI. Three hundred patients were recruited and clinical information was collected before genotyping. ABCC8 and KCNJ11 genes were analysed in all patients. Mutations in GLUD1, HADH, GCK and HNF4A genes were sought in patients with diazoxide-responsive CHI with hyperammonaemia (GLUD1), raised 3-hydroxybutyrylcarnitine and/or consanguinity (HADH), positive family history (GCK) or when CHI was diagnosed within the first week of life (HNF4A). Mutations were identified in 136/300 patients (45.3%). Mutations in ABCC8/KCNJ11 were the commonest genetic cause identified (n=109, 36.3%). Among diazoxide-unresponsive patients (n=105), mutations in ABCC8/KCNJ11 were identified in 92 (87.6%) patients, of whom 63 patients had recessively inherited mutations while four patients had dominantly inherited mutations. A paternal mutation in the ABCC8/KCNJ11 genes was identified in 23 diazoxide-unresponsive patients, of whom six had diffuse disease. Among the diazoxide-responsive patients (n=183), mutations were identified in 41 patients (22.4%). These include mutations in ABCC8/KCNJ11 (n=15), HNF4A (n=7), GLUD1 (n=16) and HADH (n=3). A genetic diagnosis was made for 45.3% of patients in this large series. Mutations in the ABCC8 gene were the commonest identifiable cause. The vast majority of patients with diazoxide-responsive CHI (77.6%) had no identifiable mutations, suggesting other genetic and/or environmental mechanisms.


An evaluation of a self-generated identification code.
We describe a self-generated coding form used in a study of HIV prevention practices of college students and provide information on the success rate of matching questionnaires over a 3-year period using the form. The data for this study were from a longitudinal study of HIV risk-reduction practices of college students. In order to match questionnaires over the 3-year study period while maintaining anonymity, participants were asked to complete a self-generated identification form at each data collection point. In the second year of the project, we were able to successfully match 74.3% of the questionnaires to those returned during the first year using 6 to 8 of the code elements on the form, and in the third year, we were able to match 73% of questionnaires to those returned in the second year. Participants for whom questionnaires matched were more likely than participants with unmatched questionnaires to be white students enrolled as underclassmen.


Subjective health complaints are not associated with tick bites or antibodies to Borrelia burgdorferi sensu lato in blood donors in western Norway: a cross-sectional study.
There is controversy about chronic health consequences of tick-borne infections, especially Lyme borreliosis. This study aims to assess whether general function, physical fitness and subjective health complaints are associated with tick bites or antibodies to Borrelia burgdorferi sensu lato in blood donors. Sera from 1,213 blood donors at four different blood banks in Sogn and Fjordane county in western Norway were obtained during January to June 2010, and analysed for specific IgG and IgM antibodies. A questionnaire including questions on tick bites, subjective health complaints, general function and physical fitness was completed. Tick bites had been experienced by 65.7% of the study population. 78 (6.4%) were positive for IgG (9.7% in men, 2.4% in women), and 69 (5.7%) for IgM (6.1% in men, 5.1% in women), verified by immunoblot. No association between number of experienced tick bites or seropositivity for Borrelia antibodies and subjective health complaints, reduced general function or reduced physical fitness was found. The results do not support any association between tick bites or Borrelia antibodies and subjective health complaints in blood donors in an endemic area for Lyme borreliosis.


Stability and in vivo behavior of Rh[16aneS4-diol]211 at complex: a potential precursor for astatine radiopharmaceuticals.
The heavy halogen (211)At is of great interest for targeted radiotherapy because it decays by the emission of short-range, high-energy α-particles. However, many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking other (211)At labeling strategies. One relatively unexplored approach is to utilize prosthetic groups based on astatinated rhodium (III) complex stabilized with a tetrathioether macrocyclic ligand - Rh[16aneS(4)-diol](211)At. The purpose of the current study was to evaluate the in vitro and in vivo stability of this complex in comparison to its iodine analog - Rh[16aneS(4)-diol](131)I. Rh[16aneS(4)-diol](211)At and Rh[16aneS(4)-diol](131)I complexes were synthesized and purified by HPLC. The stability of both complexes was evaluated in vitro by incubation in phosphate-buffered saline (PBS) and human serum at different temperatures. The in vivo behavior of the two radiohalogenated complexes was assessed by a paired-label biodistribution study in normal Balb/c mice. Both complexes were synthesized in high yield and purity. Almost no degradation was observed for Rh[16aneS(4)-diol](131)I in PBS over a 72 h incubation. The astatinated analog exhibited good stability in PBS over 14 h. A slow decline in the percentage of intact complex was observed for both tracers in human serum. In the biodistribution study, retention of (211)At in most tissues was higher than that of (131)I at all time points, especially in spleen and lungs. Renal clearance of Rh[16aneS(4)-diol](211)At and Rh[16aneS(4)-diol](131)I predominated, with 84.1 ± 2.3% and 94.6 ± 0.9% of injected dose excreted via the urine at 4 h. The Rh[16aneS(4)-diol](211)At complex might be useful for constructing prosthetic groups for the astatination of biomolecules and further studies are planned to evaluate this possibility.


Habituation in the KIII olfactory model with chemical sensor arrays.
This paper presents a novel combination of chemical sensors and the KIII model for simulating mixture perception with a habituation process triggered by local activity. Stimuli are generated by partitioning feature space with labeled lines. Pattern completion is demonstrated through coherent oscillations across granule populations using experimental odor mixtures.


Instrument-Assisted Soft Tissue Mobilization Increased Hamstring Mobility.
Limited research reveals that the use of different soft tissue mobilization techniques increases tissue mobility in different regions of the body. The purpose of this study was to determine whether there is a difference between administering instrument-assisted soft tissue mobilization (IASTM) and therapeutic cupping (TC) on hamstring tightness. Subjects attended one session wherein treatment and leg order were randomized before attending the session. A statistical analysis was completed using a 2 (intervention) × 2 (time) repeated-measures analysis of variance at α level ≤ .05. Thirty-three subjects between the age of 18-35 years old with bilateral hamstring tightness participated in this study. The IASTM and TC were administered on different legs for 5 minutes and over the entire area of the hamstring muscles. One TC was moved over the entire treatment area in a similar fashion as the IASTM. The intervention measurements included soreness numeric rating scale, Sit-n-Reach (single leg for side being tested), goniometric measurement for straight-leg hip-flexion motion, and superficial skin temperature. The timeline for data collection included: (1) intervention measurements for the first randomized leg, (2) 5-minute treatment with the first intervention treatment, (3) intervention measurements repeated for postintervention outcomes, and (4) repeat the same steps for 1 to 3 with the contralateral leg and the other intervention. There was a main effect over time for Sit-n-Reach, measurement (pre-IASTM-29.50 [8.54], post-IASTM-32.11 [8.31] and pre-TC-29.67 [8.21], post-TC-32.05 [8.25]) and goniometric measurement (pre-IASTM-83.45 [13.86], post-IASTM-92.73 [13.20] and pre-TC-83.76 [11.97], post-TC-93.67 [12.15]; P < .05). Both IASTM and TC impacted hamstring mobility during a single treatment using only an instrument-assisted soft tissue mobilization technique without any additional therapeutic intervention.


Analgesic effects of manual therapy in patients with musculoskeletal pain: a systematic review.
Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic effects of manual therapy on peripheral joints have not been systematically reviewed. A systematic review was carried out following the PRISMA-guidelines. Manual therapy was defined as any manual induced articular motion with the aim of inducing analgesic effects. Outcome measure was pain threshold. A total of 13 randomized trials were included in the review. In 10 studies a significant effect was found. Pressure pain thresholds increased following spinal or peripheral manual techniques. In three studies both a local and widespread analgesic effect was found. No significant effect was found on thermal pain threshold. Moderate evidence indicated that manual therapy increased local pressure pain thresholds in musculoskeletal pain, immediately following the intervention. No consistent result was found on remote pressure pain threshold. No significant changes occured on thermal pain threshold values. The clinical relevance of these effects remains contradictory and therefore unclear.


CE: Using Smart IV Infusion Pumps Outside of Patient Rooms.
The COVID-19 pandemic has created unique challenges for health care workers, who have demonstrated dedication, collaboration, and innovation in response. In this article, the authors describe an important nursing innovation they employed at Montefiore Medical Center in the Bronx, New York, during the spring 2020 COVID-19 surge: the relocation of smart IV infusion pumps outside of patient rooms. The goals of this innovation were to improve delivery of care, conserve personal protective equipment, limit the spread of the virus, and protect staff from exposure. The authors discuss the initial concerns that arose regarding the safety and efficacy of this practice; the research they conducted with other colleagues in nursing, pharmacy, infection control, and patient safety in the face of scant clinical literature relevant to the difficult circumstances the pandemic created; and the strategies they ultimately employed to ensure that this practice maintained safety and efficacy.


Phylogenetic analysis of Ruminococcus flavefaciens, the type species of the genus Ruminococcus, does not support the reclassification of Streptococcus hansenii and Peptostreptococcus productus as ruminococci.
The 16S rRNA gene sequence of the type strain of Ruminococcus flavefaciens, the type species of the genus Ruminococcus, was determined by PCR direct sequencing. A comparative sequence analysis showed that R. flavefaciens is phylogenetically related to a small cluster (cluster IV of Collins et al. [M. D. Collins, P. A. Lawson, A. Willems, J. J. Cordoba, J. Fernandez-Garayzabal, P. Garcia, J. Cai, H. Hippe, and J. A. E. Farrow, Int. J. Syst. Bacteriol. 44:812-826, 1994]) of organisms which includes several Clostridium and Eubacterium species. R. flavefaciens was found to be phylogenetically only remotely related to Ruminococcus gnavus, Ruminococcus torques, Peptostreptococcus productus, and Streptococcus hansenii. These findings demonstrate that the genus Ruminococcus is not a monophyletic group, and the proposed transfer of P. productus and S. hansenii to this genus (T. Ezaki, N. Li, Y. Hashimoto, H. Miura, and H. Yamamoto, Int. J. Syst. Bacteriol. 44:130-136, 1994) is not supported.


Molecular imaging of aberrant crypt foci in the human colon targeting glutathione S-transferase P1-1.
Aberrant crypt foci (ACF), the earliest precursor lesion of colorectal cancers (CRCs), are a good surrogate marker for CRC risk stratification and chemoprevention. However, the conventional ACF detection method with dye-spraying by magnifying colonoscopy is labor- and skill-intensive. We sought to identify rat and human ACF using a fluorescent imaging technique that targets a molecule specific for ACF. We found that glutathione S-transferase (GST) P1-1 was overexpressed in ACF tissues in a screening experiment. We then synthesized the fluorogenic probe, DNAT-Me, which is fluorescently quenched but is activated by GSTP1-1. A CRC cell line incubated with DNAT-Me showed strong fluorescence in the cytosol. Fluorescence intensities correlated significantly with GST activities in cancer cell lines. When we sprayed DNAT-Me onto colorectal mucosa excised from azoxymethane-treated rats and surgically resected from CRC patients, ACF with strong fluorescent signals were clearly observed. The ACF number determined by postoperative DNAT-Me imaging was almost identical to that determined by preoperative methylene blue staining. The signal-to-noise ratio for ACF in DNAT-Me images was significantly higher than that in methylene blue staining. Thus, we sensitively visualized ACF on rat and human colorectal mucosa by using a GST-activated fluorogenic probe without dye-spraying and magnifying colonoscopy.


Cyclopiazonic acid production by Aspergillus flavus and its effects on broiler chickens.
Cyclopiazonic acid (CPA) was purified from cultures of Aspergillus flavus, and ca. 14 g of the toxin was collected for use in feeding studies. Chicken rations were artificially contaminated with purified CPA at concentrations of 10, 50, and 100 ppm (microgram/g) and fed ad libitum to eight groups of chickens for 7 weeks. Chickens receiving feed with 100 ppm of CPA had high mortality, decreased weight gain, and poor feed conversion when compared with birds receiving other doses. Postmortem examination showed that chickens fed the two greatest doses of CPA had proventricular lesions characterized by mucosal erosion and hyperemia (100 ppm) and by thick mucosa and dilated proventricular lumens (50 ppm). Birds given 100 ppm of CPA in feed also had numerous yellow foci in their livers and spleens. Microscopic examination of tissues of birds that received 100 ppm of CPA revealed ulcerative proventriculitis, mucosal necrosis in the gizzard, and hepatic and splenic necrosis and inflammation. Birds given 50 ppm of CPA had hyperplasia of the proventricular mucosal epithelium. Birds given 10 ppm of CPA and control birds had no significant treatment-related lesions.


Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo.
The onset of distant organ metastasis from primary breast cancer marks the transition to a stage IV diagnosis. Standard imaging modalities often detect distant metastasis when the burden of disease is high, underscoring the need for improved methods of detection to allow for interventions that would impede disease progression. Here, microporous poly(ε-caprolactone) scaffolds were developed that capture early metastatic cells and thus serve as a sentinel for early detection. These scaffolds were used to characterize the dynamic immune response to the implant spanning the acute and chronic foreign body response. The immune cell composition had stabilized at the scaffold after approximately 1 month and changed dramatically within days to weeks after tumor inoculation, with CD11b(+)Gr1(hi)Ly6C(-) cells having the greatest increase in abundance. Implanted scaffolds recruited metastatic cancer cells that were inoculated into the mammary fat pad in vivo, which also significantly reduced tumor burden in the liver and brain. Additionally, cancer cells could be detected using a label-free imaging modality termed inverse spectroscopic optical coherence tomography, and we tested the hypothesis that subsequent removal of the primary tumor after early detection would enhance survival. Surgical removal of the primary tumor following cancer cell detection in the scaffold significantly improved disease-specific survival. The enhanced disease-specific survival was associated with a systemic reduction in the CD11b(+)Gr1(hi)Ly6C(-) cells as a consequence of the implant, which was further supported by Gr-1 depletion studies. Implementation of the scaffold may provide diagnostic and therapeutic options for cancer patients in both the high-risk and adjuvant treatment settings. Cancer Res; 76(18); 5209-18. ©2016 AACR.


Modulation of embryonic chick motoneuron glutamate sensitivity by interneurons and agonists.
Embryonic chick motoneurons grown in culture together with other spinal cord cells are more sensitive to L-glutamate than are sorted motoneurons grown in isolation. After 6 d in vitro, the difference in peak sensitivity reached 6-fold. Comparable increases in aspartate and kainate currents were observed, indicating that both G1 and G2 amino acid receptors were affected. Elimination of proliferating non-neuronal cells from mixed spinal cord cell cultures by addition of cytosine arabinoside (ara C) did not prevent the increase in motoneuron chemosensitivity, so the induction is probably due to the presence of interneurons. In contrast to their effect on glutamate response, interneurons did not affect the sensitivity of motoneurons to the inhibitory neurotransmitters GABA and glycine. Glutamate receptors expressed by sorted and unsorted motoneurons are identical in terms of their ED50, reversal potential, mean channel open time, and conductance, implying that the increased sensitivity of motoneurons in mixed cultures is due to an increase in the number of open channels. In addition to an increase in the number of channels, the distribution of glutamate sensitivity over the surface of individual motoneurons was altered in interneuron-containing cultures. The sensitivity of isolated motoneurons was greatest at the soma and decreased with distance along major processes, but the sites of highest sensitivity on motoneurons in mixed cultures occurred along their processes. Sharp peaks identified by focal iontophoresis of glutamate were separated by areas of lower sensitivity. The inductive effect of interneurons cannot be due to glutamate, the most likely excitatory interneuron-motoneuron transmitter in 6 d chick cultures.(ABSTRACT TRUNCATED AT 250 WORDS)


Anthropometric Indexes for Predicting High Blood Pressure in Vietnamese Adults: A Cross-Sectional Study.
The rate of hypertension and obesity is increasing in Vietnamese society. This study aimed to focus on assessing the relationship between anthropometric indexes (body mass index (BMI), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR)) and high blood pressure to determine which is the best predictor for high blood pressure among adults over 18 years in Vietnam. A cross-sectional study of 1636 people was conducted. People who were over 18 years old, healthy or had hyperlipidemia and on the treatment were recruited. Patients with cancer, heart disease, diabetes, kidney disease, and hypertension were excluded. Information on demographics, smoking and drinking habits, weight, height, waist circumference, and blood pressure was collected. Areas under receiver operating characteristic curves (AUCs) were examined to determine the predictability of anthropometric indicators for high blood pressure in men and women. Logistic regression analysis, stratified by gender, was performed to examine the association between anthropometric indexes and high blood pressure. In this study, the percentage of people with high blood pressure was 10.51%. The AUC for the WHtR was significantly greater than for the BMI for both genders. Logistic regression demonstrated that only WHtR had a significant positive association with high blood pressure among women. The optimal WHtR cut-off value for predicting high blood pressure in men and women were 0.47 and 0.50, respectively. Among the indicators analyzed in this study, WHtR was the best for the predicting of the presence of high blood pressure, in both men and women. However, WHtR could only explain the changes of high blood pressure in women.


Neuroimaging the temporal dynamics of human avoidance to sustained threat.
Many forms of human psychopathology are characterized by sustained negative emotional responses to threat and chronic behavioral avoidance, implicating avoidance as a potential transdiagnostic factor. Evidence from both nonhuman neurophysiological and human neuroimaging studies suggests a distributed frontal-limbic-striatal brain network supports avoidance. However, our understanding of the temporal dynamics of the network to sustained threat that prompts sustained avoidance is limited. To address this issue, 17 adults were given extensive training on a modified free-operant avoidance task in which button pressing avoided money loss during a sustained threat period. Subsequently, subjects underwent functional magnetic resonance imaging while completing the avoidance task. In our regions of interest, we observed phasic, rather than sustained, activation during sustained threat in dorsolateral and inferior frontal regions, anterior and dorsal cingulate, ventral striatum and regions associated with emotion, including the amygdala, insula, substantia nigra and bed nucleus of the stria terminalis complex. Moreover, trait levels of experiential avoidance were negatively correlated with insula, hippocampal and amygdala activation. These findings suggest knowledge that one can consistently avoid aversive outcomes is not associated with decreased threat-related responses and that individuals with greater experiential avoidance exhibit reduced reactivity to initial threat. Implications for understanding brain mechanisms supporting human avoidance and psychological theories of avoidance are discussed.


Longitudinal Multi-Trait-State-Method Model Using Ordinal Data.
Multi-trait multi-method (MTMM) models provide a way to assess convergent and discriminant validity when multiple traits are measured by multiple methods. In recent years, longitudinal extensions of MTMM models have been proposed in the structural equation modeling framework to evaluate whether and how the trait as well as method factors change over time. We propose a novel longitudinal ordinal MTMM model that can be used to effectively distinguish volatile "state" processes from "trait" processes that tend to remain stable and invariant over time. The proposed model, termed a longitudinal multi-trait-state-method (LM-TSM) model, combines 3 key modeling components: (a) a measurement model for ordinal data, (b) a vector autoregressive moving average model at the latent level to examine changes in the state as well as the method factors over time, and (c) a second-order factor-analytic model to capture time-invariant traits as shared variances among the state factors across all measurement occasions. Data from the Affective Dynamics and Individual Differences (ADID; Emotions and Dynamic Systems Laboratory, 2010 ) study was used to illustrate the proposed longitudinal LM-TSM model. Methodological issues associated with fitting the LM-TSM model are discussed.


Pitch Counts in Youth Baseball and Softball: A Historical Review.
Pitching injuries are getting increased attention in the mass media. Many references are made to pitch counts and the role they play in injury prevention. The original purpose of regulating the pitch count in youth baseball was to reduce injury and fatigue to pitchers. This article reviews the history and development of the pitch count limit in baseball, the effect it has had on injury, and the evidence regarding injury rates on softball windmill pitching. Literature search through PubMed, mass media, and organizational Web sites through June 2015. Pitch count limits and rest recommendations were introduced in 1996 after a survey of 28 orthopedic surgeons and baseball coaches showed injuries to baseball pitchers' arms were believed to be from the number of pitches thrown. Follow-up research led to revised recommendations with more detailed guidelines in 2006. Since that time, data show a relationship between innings pitched and upper extremity injury, but pitch type has not clearly been shown to affect injury rates. Current surveys of coaches and players show that coaches, parents, and athletes often do not adhere to these guidelines. There are no pitch count guidelines currently available in softball. The increase in participation in youth baseball and softball with an emphasis on early sport specialization in youth sports activities suggests that there will continue to be a rise in injury rates to young throwers. The published pitch counts are likely to positively affect injury rates but must be adhered to by athletes, coaches, and parents.


Opinions of South African physiotherapists on gross anatomy education for physiotherapy students.
Physiotherapists know the depth of gross anatomical knowledge required for safe and effective clinical practice. They can offer insightful opinions on inclusions for and teaching of an anatomy curriculum for physiotherapy students. The aim of this study was to gather opinions of physiotherapists as to what they perceive as necessary anatomy curricular content for undergraduate physiotherapy students and identify pedagogy that should be used. A qualitative methodology using a grounded theory approach incorporating semi-structured interviews was utilised in this study. Theoretical sampling was used to identify representative South African physiotherapists. An inductive process, using continuous manual analysis of data by two independent coders, was undertaken. Data were collapsed until themes were identified. Triangulation and other strategies for trustworthiness of data were instituted. Theoretical saturation was reached after five focus groups (n = 32). Demographical information indicated physiotherapists of all age groups and both genders working in diversified clinical areas. Seven themes were identified and incorporated information from 'structure', 'content' and 'pedagogy' for anatomy programmes to the psychological impact of course aspects on a student's psyche. Vertical integration of anatomy into later preclinical years, incorporation of physiotherapists to teach anatomy, a 'physiotherapist personality' and 'anatomy know how' for clinical practice were included. Opinions of physiotherapists are important in identifying curricular and teaching considerations that can be incorporated into an anatomy programme designed for physiotherapy students. Targeted anatomy education for physiotherapy students can aid learning and retention of anatomical knowledge necessary for effective and safe clinical practice.


Dual Effects of 3-epi-betulin from Daphniphyllum glaucescens in Suppressing SARS-CoV-2-Induced Inflammation and Inhibiting Virus Entry.
The continuous emergence of SARS-CoV-2 variants has led to a protracted global COVID-19 pandemic with significant impacts on public health and global economy. While there are currently available SARS-CoV-2 vaccines and therapeutics, most of the FDA-approved antiviral agents directly target viral proteins. However, inflammation is the initial immune pathogenesis induced by SARS-CoV-2 infection, there is still a need to find additional agents that can control the virus in the early stages of infection to alleviate disease progression for the next pandemic. Here, we find that both the spike protein and its receptor CD147 are crucial for inducing inflammation by SARS-CoV-2 in THP-1 monocytic cells. Moreover, we find that 3-epi-betulin, isolated from Daphniphyllum glaucescens, reduces the level of proinflammatory cytokines induced by SARS-CoV-2, consequently resulting in a decreased viral RNA accumulation and plaque formation. In addition, 3-epi-betulin displays a broad-spectrum inhibition of entry of SARS-CoV-2 pseudoviruses, including Alpha (B.1.1.7), Eplison (B.1.429), Gamma (P1), Delta (B.1.617.2) and Omicron (BA.1). Moreover, 3-epi-betulin potently inhibits SARS-CoV-2 infection with an EC50 of <20 μM in Calu-3 lung epithelial cells. Bioinformatic analysis reveals the chemical interaction between the 3-epi-betulin and the spike protein, along with the critical amino acid residues in the spike protein that contribute to the inhibitory activity of 3-epi-betulin against virus entry. Taken together, our results suggest that 3-epi-betulin exhibits dual effect: it reduces SARS-CoV-2-induced inflammation and inhibits virus entry, positioning it as a potential antiviral agent against SARS-CoV-2.


Measuring immigrant wage growth using matched CPS files.
Cross-sectional estimates of immigrant wage growth have painted an optimistic picture of the ability of immigrants to adapt to the U.S. labor market: Studies using cross-sectional data have generally found the wage growth of immigrants to exceed that of the native born. This optimistic picture of immigrant economic assimilation was challenged by the important finding that compared to earlier immigrant cohorts, recent immigrants started at much lower wages. As such, the high wage growth of immigrants relative to the native born measured in cross-sectional data may simply be the spurious result of declining immigrant earnings ability. In this paper, we match Current Population Survey samples so that the wages of individual immigrant and native-born men can be followed for one year. We find that the wage growth of immigrants does exceed that of the native born. The general finding of faster immigrant wage growth also holds when imposing the foreign-born geographic distribution upon natives, but not when imposing the native-born geographic distribution on the foreign born-a result consistent with some theories of immigrant assimilation. In each comparison, however, the actual wage growth of immigrants relative to natives is similar to the predictions of cross-sectional regressions. This similarity suggests that either there is no cohort quality bias in the cross-sectional estimates of immigrant wage growth, or that there has been a coincidental increase in immigrant wage growth as the entry wages of immigrants have fallen.


Urinary polyaromatic hydrocarbons are associated with adult celiac disease and kidney stones: USA NHANES, 2011-2012.
Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons (PAH) were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols, and pesticides. Therefore, it was aimed to study the relationships of urinary PAH and adult digestive conditions using a large human sample in a national and population-based study in recent years. Data was retrieved from the US National Health and Nutrition Examination Surveys, 2011-2012 including demographics, self-reported health conditions, and urinary PAH. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary 4-hydroxyphenanthrene was significantly associated with celiac disease (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.14-2.26, P = 0.009). In addition, urinary 2-hydroxyfluorene (OR 1.35, 95% CI 1.02-1.78, P = 0.038), 3-hydroxyfluorene (OR 1.35, 95% CI 1.07-1.70, P = 0.015), 1-hydroxyphenanthrene (OR 1.48, 95% CI 1.08-2.03, P = 0.017), 1-hydroxypyrene (OR 1.36, 95% CI 1.05-1.77, P = 0.023), and 2-hydroxynapthalene (OR 1.25, 95% CI 1.00-1.58, P = 0.054) were significantly associated with kidney stones, although not necessarily failing kidney. There were no statistically significant associations observed in the relationship of urinary PAH and liver problems, although higher levels of PAHs were observed. Urinary PAHs are associated with adult digestive conditions, although the causality cannot be established. From the research perspective, longitudinal monitoring from observational studies and experimental research understanding mechanism would be suggested. Regulation of minimizing PAHs exposure might need to be considered in future health and environmental policies.


The changing epidemiology of varicella and herpes zoster in Hong Kong before universal varicella vaccination in 2014.
In Hong Kong, universal varicella vaccination started in July 2014. Before this, children could receive varicella vaccine via the private market. We analysed the epidemiology of varicella and zoster before universal vaccination. We estimated varicella vaccination coverage through surveys in preschool children. We estimated the burden of varicella and zoster with varicella notifications from 1999/00 to 2013/14, Accident and Emergency Department (A&E) attendance and inpatient admissions to public hospitals from 2004/05 to 2013/14. We fitted a catalytic model to serological data on antibodies against varicella-zoster virus to estimate the force of infection. We found that varicella vaccination coverage gradually increased to about 50% before programme inception. In children younger than 5 years, the annual rate of varicella notifications, varicella admission and zoster A&E attendance generally declined. The annual notification, A&E attendance and hospitalisation rate of varicella and zoster generally increased for individuals between 10 and 59 years old. Varicella serology indicated an age shift during the study period towards a higher proportion of infections in slightly older individuals, but the change was most notable before vaccine licensure. In conclusion, we observed a shift in the burden of varicella to slightly older age groups with a corresponding increase in incidence but it cannot necessarily be attributed to private market vaccine coverage alone. Increasing varicella vaccination uptake in the private market might affect varicella transmission and epidemiology, but not to the level of interrupting transmission.


High-resolution scanning electron-microscopic studies on the three-dimensional structure of mitochondria and sarcoplasmic reticulum in the different twitch muscle fibers of the frog.
The three-dimensional structure of the mitochondria and sarcoplasmic reticulum (SR) in the three types of twitch fibers, i.e., the red, white and intermediate skeletal muscle fibers, of the vastus lateralis muscle of the Japanese meadow frog (Rana nigromaculata nigromaculata Hallowell) was examined by high resolution scanning electron microscopy, after removal of the cytoplasmic matrices. The small red fibers have numerous mitochondrial columns of large diameter, while the large white fibers have a small number of mitochondrial columns of small diameter. In the medium-size intermediate fibers, the number and diameter of the mitochondrial columns are intermediate between those of the red and white fibers. In all three types of fibers, the terminal cisternae and transverse tubules form triads at the level of each Z-line. The thick terminal cisternae continue into much thinner flat intermediate cisternae, through a transitional part where a row of tiny indentations can be observed. Numerous slender longitudinal tubules originating from the intermediate cisternae, extend longitudinally or obliquely and form elongated oval networks of various sizes in front of the A-band, then fuse to form the H-band collar (fenestrated collar) around the myofibrils. On the surface of the H-band collar, small fenestrations as well as tiny hollows are seen. The three-dimensional structure of SR is basically the same in all three muscle fiber-types. However, the SR is sparse on the surface of mitochondria, so the mitochondria-rich red fiber has a smaller total volume of SR than the mitochondria-poor white fiber. The volume of SR of the intermediate fiber is intermediate between other the two.


Proton Pump Inhibitor Ameliorates Taste Disturbance among Patients with Laryngopharyngeal Reflux: A Randomized Controlled Study.
Patients with laryngopharyngeal reflux (LPR) were reported to suffer from hypogeusia that affects quality of life. Proton pump inhibitor (PPI) is a useful drug in the treatment of LPR, but its effect on hypogeusia is not known. We therefore assessed the effects of PPI or a histamine H2 receptor antagonist (H2 blocker) on hypogeusia among patients with LPR. Both PPI and H2 blocker could inhibit acid reflux. LPR was diagnosed with reflux finding score and reflux symptom index. The visual analogue scale (VAS) of taste disturbance symptoms and the gustatory tests were assessed before and 8 weeks after treatment with esomeprazole, a PPI (20 patients, aged 50.0 ± 1.7 years) or famotidine, a H2 blocker (20 patients, aged 47.1 ± 1.8 years). There were no significant differences in VAS scores and recognition thresholds for four basic tastes between the two groups before treatment. Only PPI therapy significantly decreased the VAS scores, suggesting the improvement of taste perception. Moreover, PPI therapy significantly decreased recognition thresholds for bitter taste in the anterior tongue (chorda tympani nerve area) and the thresholds in the posterior tongue (glossopharyngeal nerve area) for salty, sour, and bitter tastes. By contrast, H2-blocker therapy caused no significant changes of thresholds in the anterior tongue, but improved the threshold only for bitter in the posterior tongue, the value of which was however significantly higher than that in PPI group. In conclusion, PPI could ameliorate hypogeusia by improving bitter, salty, and sour tastes among patients with LPR.


White Matter Stroke Induces a Unique Oligo-Astrocyte Niche That Inhibits Recovery.
Subcortical white matter stroke is a common stroke subtype. White matter stroke stimulates adjacent oligodendrocyte progenitor cells (OPCs) to divide and migrate to the lesion, but stroke OPCs have only a limited differentiation into mature oligodendrocytes. To understand the molecular systems that are active in OPC responses in white matter stroke, OPCs were virally labeled and laser-captured in the region of partial damage adjacent to the infarct in male mice. RNAseq indicates two distinct OPC transcriptomes associated with the proliferative and limited-regeneration phases of OPCs after stroke. Molecular pathways related to nuclear receptor activation, ECM turnover, and lipid biosynthesis are activated during proliferative OPC phases after stroke; inflammatory and growth factor signaling is activated in the later stage of limited OPC differentiation. Within ECM proteins, Matrilin-2 is induced early after stroke and then rapidly downregulated. Prediction of upstream regulators of the OPC stroke transcriptome identifies several candidate molecules, including Inhibin A-a negative regulator of Matrilin-2. Inhibin A is induced in reactive astrocytes after stroke, including in humans. In functional assays, Matrilin-2 induces OPC differentiation, and Inhibin A inhibits OPC Matrilin-2 expression and inhibits OPC differentiation. In vivo, Matrilin-2 promotes motor recovery after white matter stroke, and promotes OPC differentiation and ultrastructural evidence of remyelination. These studies show that white matter stroke induces an initial proliferative and reparative response in OPCs, but this is blocked by a local cellular niche where reactive astrocytes secrete Inhibin A, downregulating Matrilin-2 and blocking myelin repair and recovery.SIGNIFICANCE STATEMENT Stroke in the cerebral white matter of the brain is common. The biology of damage and recovery in this stroke subtype are not well defined. These studies use cell-specific RNA sequencing and gain-of-function studies to show that white matter stroke induces a glial signaling niche, present in both humans and mice, between reactive astrocytes and oligodendrocyte progenitor cells. Astrocyte secretion of Inhibin A and downregulation of oligodendrocyte precursor production of Matrilin-2 limit OPC differentiation, tissue repair, and recovery in this disease.


Genome-Wide Linkage Mapping of QTL for Adult-Plant Resistance to Stripe Rust in a Chinese Wheat Population Linmai 2 × Zhong 892.
Stripe rust is one of the most devastating diseases of wheat (Triticum aestivum) worldwide. Adult-plant resistance (APR) is an efficient approach to provide long-term protection of wheat from the disease. The Chinese winter wheat cultivar Zhong 892 has a moderate level of APR to stripe rust in the field. To determine the inheritance of the APR resistance in this cultivar, 273 F6 recombinant inbred lines (RILs) were developed from a cross between Linmai 2 and Zhong 892. The RILs were evaluated for maximum disease severity (MDS) in two sites during the 2011-2012, 2012-2013 and 2013-2014 cropping seasons, providing data for five environments. Illumina 90k SNP (single nucleotide polymorphism) chips were used to genotype the RILs and their parents. Composite interval mapping (CIM) detected eight QTL, namely QYr.caas-2AL, QYr.caas-2BL.3, QYr.caas-3AS, QYr.caas-3BS, QYr.caas-5DL, QYr.caas-6AL, QYr.caas-7AL and QYr.caas-7DS.1, respectively. All except QYr.caas-2BL.3 resistance alleles were contributed by Zhong 892. QYr.caas-3AS and QYr.caas-3BS conferred stable resistance to stripe rust in all environments, explaining 6.2-17.4% and 5.0-11.5% of the phenotypic variances, respectively. The genome scan of SNP sequences tightly linked to QTL for APR against annotated proteins in wheat and related cereals genomes identified two candidate genes (autophagy-related gene and disease resistance gene RGA1), significantly associated with stripe rust resistance. These QTL and their closely linked SNP markers, in combination with kompetitive allele specific PCR (KASP) technology, are potentially useful for improving stripe rust resistances in wheat breeding.


Reducing Geometric Uncertainty in Computational Hemodynamics by Deep Learning-Assisted Parallel-Chain MCMC.
Computational hemodynamic modeling has been widely used in cardiovascular research and healthcare. However, the reliability of model predictions is largely dependent on the uncertainties of modeling parameters and boundary conditions, which should be carefully quantified and further reduced with available measurements. In this work, we focus on propagating and reducing the uncertainty of vascular geometries within a Bayesian framework. A novel deep learning (DL)-assisted parallel Markov chain Monte Carlo (MCMC) method is presented to enable efficient Bayesian posterior sampling and geometric uncertainty reduction. A DL model is built to approximate the geometry-to-hemodynamic map, which is trained actively using online data collected from parallel MCMC chains and utilized for early rejection of unlikely proposals to facilitate convergence with less expensive full-order model evaluations. Numerical studies on two-dimensional aortic flows are conducted to demonstrate the effectiveness and merit of the proposed method.


Using nature-based rehabilitation to restart a stalled process of rehabilitation in individuals with stress-related mental illness.
After a period of decrease, sick leave in Sweden due to psychiatric diagnoses is on the increase. The lack of established rehabilitation programmes for patients with stress-related mental disorders (SRMD) has opened up for the use of garden/nature in a multimodal rehabilitation context (Nature-Based Rehabilitation, NBR). Region Västra Götaland (VGR) started an NBR to offer additional rehabilitation for its employees on long-term sick leave due to SRMD, where initial care had not been sufficient. The aim was to explore whether the mental health and well-being of NBR participants had improved at the end of the NBR and at three follow-ups, and to explore the development of sick leave and health care utilization according to the NBR model (n = 57) and an occupational health service (OHS) model (n = 45). Self-assessment instruments for measuring burnout, depression, anxiety and wellbeing, and data from regional and national registers were used. Results showed decreased scores on burnout, depression and anxiety, and increased well-being scores and significantly reduced health care utilization in the NBR group. A large movement from ordinary sickness benefit to rehabilitation benefit was observed, which was not observed in the OHS group. The two groups were in different rehabilitation phases, which limited comparisons. The results point to beneficial effects of using NBR for this patient group and for enhancing a stalled rehabilitation process.


Effects of Allopurinol on Arterial Stiffness: A Meta-Analysis of Randomized Controlled Trials.
BACKGROUND Several studies have tested the effects of allopurinol on arterial stiffness, but the results have been inconclusive. We aimed to conduct a meta-analysis to investigate the impacts of allopurinol treatment on arterial stiffness, as measured by pulse wave velocity (PWV) and augmentation index (AIx). MATERIAL AND METHODS Randomized controlled trials (RCTs) assessing the effects of allopurinol on arterial stiffness were identified through searching PubMed, Web of Science, EMBASE, the Cochrane Library for Central Register of Clinical Trials, and China National Knowledge Infrastructure up to December 2015. The primary endpoints were the change of PWV and AIx after allopurinol treatment. The weighted mean difference (WMD) or standardized mean difference (SMD) and the 95% confidence interval (CI) of each study were pooled for meta-analysis. RESULTS A total of 11 RCTs met the inclusion criteria and were included in the final meta-analysis. Eight RCTs with 1,111 patients were pooled for PWV; eight RCTs with 397 patients were pooled for PWV. Allopurinol administration did not significantly change PWV (WMD=-0.19 m/s, 95% CI: -0.49 to 0.12, Z=1.21, p=0.23), but significantly reduced AIx (SMD=-0.34, 95% CI: -0.54 to -0.14, Z=3.35, p=0.0008). CONCLUSIONS Although our meta-analysis showed some favorable effects of allopurinol treatment on improving AIx, its impact on arterial stiffness must be tested in more large-scale RCTs.


Peculiar respiratory response observed during sleep-onset REM sleep of an infant with Ondine's curse.
We treated an infant with congenital central hypoventilation syndrome ("Ondine's curse"). She was cyanotic and given ventilatory support at the first hour after birth. An investigation of sleep state and respiration performed at the age of 3 months led to this diagnosis. Hypoventilation persisted in all sleep stages, with the most severely reduced tidal volumes occurring during delta-wave sleep (stages 3 and 4). In addition, severe secondary reduction in tidal volumes occurred in sleep-onset REM sleep. This phenomenon was absent in non sleep-onset REM sleep. At 4 months of age, her respiratory treatment was successfully converted to positive-pressure ventilation via a nasal mask, thus avoiding tracheotomy. This transition to noninvasive ventilatory support dramatically improved her quality of life during wakefulness. This report may be a clue to discuss the function of sleep-onset REM sleep seen in the early stage of life and suggests that nasal mask ventilation is a viable option in selected cases with congenital central hypoventilation syndrome (CCHS).


Contactin-1 Is Reduced in Cerebrospinal Fluid of Parkinson's Disease Patients and Is Present within Lewy Bodies.
Synaptic degeneration is an early phenomenon in Parkinson's disease (PD) pathogenesis. We aimed to investigate whether levels of synaptic proteins contactin-1 and contactin-2 in cerebrospinal fluid (CSF) of PD patients are reduced compared to dementia with Lewy bodies (DLB) patients and controls and to evaluate their relationship with α-synuclein aggregation. Contactin-1 and -2 were measured in CSF from PD patients (n = 58), DLB patients (n = 72) and age-matched controls (n = 90). Contactin concentration differences between diagnostic groups were assessed by general linear models adjusted for age and sex. Contactin immunoreactivity was characterized in postmortem substantia nigra, hippocampus and entorhinal cortex tissue of PD patients (n = 4) and controls (n = 4), and its relation to α-syn aggregation was evaluated using confocal laser scanning microscopy. Contactin-1 levels were lower in PD patients (42 (36-49) pg/mL) compared to controls (52 (44-58) pg/mL, p = 0.003) and DLB patients (56 (46-67) pg/mL, p = 0.001). Contactin-2 levels were similar across all diagnostic groups. Within the PD patient group, contactin-1 correlated with t-α-syn, tTau and pTau (r = 0.30-0.50, p < 0.05), whereas contactin-2 only correlated with t-α-syn (r = 0.34, p = 0.03). Contactin-1 and -2 were observed within nigral and cortical Lewy bodies and clustered within bulgy Lewy neurites in PD brains. A decrease in CSF contactin-1 may reflect synaptic degeneration underlying Lewy body pathology in PD.


Macronutrient balancing in free-ranging populations of moose.
At northern latitudes, large spatial and temporal variation in the nutritional composition of available foods poses challenges to wild herbivores trying to satisfy their nutrient requirements. Studies conducted in mostly captive settings have shown that animals from a variety of taxonomic groups deal with this challenge by adjusting the amounts and proportions of available food combinations to achieve a target nutrient balance. In this study, we used proportions-based nutritional geometry to analyze the nutritional composition of rumen samples collected in winter from 481 moose (Alces alces) in southern Sweden and examine whether free-ranging moose show comparable patterns of nutrient balancing. Our main hypothesis was that wild moose actively regulate their rumen nutrient composition to offset ecologically imposed variation in the nutritional composition of available foods. To test this, we assessed the macronutritional composition (protein, carbohydrates, and lipids) of rumen contents and commonly eaten foods, including supplementary feed, across populations with contrasting winter diets, spanning an area of approximately 10,000 km2. Our results suggest that moose balanced the macronutrient composition of their rumen, with the rumen contents having consistently similar proportional relationship between protein and nonstructural carbohydrates, despite differences in available (and eaten) foods. Furthermore, we found that rumen macronutrient balance was tightly related to ingested levels of dietary fiber (cellulose and hemicellulose), such that the greater the fiber content, the less protein was present in the rumen compared with nonstructural carbohydrates. Our results also suggest that moose benefit from access to a greater variety of trees, shrubs, herbs, and grasses, which provides them with a larger nutritional space to maneuver within. Our findings provide novel theoretical insights into a model species for ungulate nutritional ecology, while also generating data of direct relevance to wildlife and forest management, such as silvicultural or supplementary feeding practices.


Policy responses to HIV/AIDS in Central Asia.
The countries of Central Asia (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan) are confronted with one of the fastest growing HIV/AIDS epidemics worldwide, largely driven through injecting drug use. This article, based on a review of academic and grey literature, explores how they have responded. We find major similarities and differences across the region. At one extreme is Turkmenistan, which denies that there is any problem, does not offer harm reduction services or HIV/AIDS treatment and does not report any meaningful data to the international community. Uzbekistan is also pretty closed to outside influences, has discontinued its opioid substitution project and shares with Turkmenistan the legal prohibition of male-to-male sex. Kyrgyzstan originally led many progressive approaches in the region and, like neighbouring Tajikistan, has received substantial assistance by international agencies, in particular the Global Fund. Kazakhstan, with a much higher gross domestic product per capita, has taken on the financing of harm reduction activities through its national budget and has liberalised its drug policies. Yet, across the region punitive approaches to injecting drug use and people living with HIV/AIDS persist as do stigma and discrimination, while coverage with harm reduction programmes and treatment services is still low although with substantial variation across countries.


Circular dichroism and magnetic circular dichroism studies of the biferrous form of the R2 subunit of ribonucleotide reductase from mouse: comparison to the R2 from Escherichia coli and other binuclear ferrous enzymes.
Ribonucleotide reductase (RNR) catalyzes the synthesis of the four deoxyribonucleotides needed for DNA synthesis and repair in living organisms. The reduced [Fe(II)Fe(II)] form of the model mammalian enzyme, mouse RNR R2, has been studied using a combination of circular dichroism (CD), magnetic circular dichroism (MCD), and variable-temperature variable-field (VTVH) MCD spectroscopies. Titrations of ferrous ion to the apo-enzyme have been performed and analyzed to investigate the metal binding affinity of the metal-binding site. Spectral features of individual iron sites have been analyzed to obtain detailed geometric and electronic structural information. VTVH MCD data have been collected and analyzed using two complementary models to obtain detailed ground state information including the zero-field splitting (ZFS) of both ferrous centers and the exchange coupling (J) between the two sites. These ground and excited state results provide a complete description of the biferrous site of mouse R2. The biferrous site consists of one 4- and one 5-coordinate iron, with positive and negative ZFS values, respectively. Weak exchange coupling between the two ferrous centers is present, consistent with having carboxylate bridges. The two sites have highly cooperative and weak metal binding affinities. This may be a novel regulatory mechanism for RNR. These results are compared with those from reduced Escherichia coli R2 and reduced acyl-carrier protein Delta(9) desaturase to correlate to similarities and differences in their dioxygen reactivity.


Effect of telecare management on pain and depression in patients with cancer: a randomized trial.
Pain and depression are 2 of the most prevalent and treatable cancer-related symptoms, yet they frequently go unrecognized, undertreated, or both. To determine whether centralized telephone-based care management coupled with automated symptom monitoring can improve depression and pain in patients with cancer. Randomized controlled trial conducted in 16 community-based urban and rural oncology practices involved in the Indiana Cancer Pain and Depression (INCPAD) trial. Recruitment occurred from March 2006 through August 2008 and follow-up concluded in August 2009. The participating patients had depression (Patient Health Questionnaire-9 score > or = 10), cancer-related pain (Brief Pain Inventory [BPI] worst pain score > or = 6), or both. The 202 patients randomly assigned to receive the intervention and 203 to receive usual care were stratified by symptom type. Patients in the intervention group received centralized telecare management by a nurse-physician specialist team coupled with automated home-based symptom monitoring by interactive voice recording or Internet. Blinded assessment at baseline and at months 1, 3, 6, and 12 for depression (20-item Hopkins Symptom Checklist [HSCL-20]) and pain (BPI) severity. Of the 405 participants enrolled in the study, 131 had depression only, 96 had pain only, and 178 had both depression and pain. Of the 274 patients with pain, 137 patients in the intervention group had greater improvements in BPI pain severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical pain responder (> or = 30% decrease in BPI) than the 137 patients in the usual-care group (P < .001 for both). Similarly, of the 309 patients with depression, the 154 patients in the intervention group had greater improvements in HSCL-20 depression severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical depression responder (> or = 50% decrease in HSCL) than the 155 patients in the usual care group (P < .001 for both). The standardized effect size for between-group differences at 3 and 12 months was 0.67 (95% confidence interval [CI], 0.33-1.02) and 0.39 (95% CI, 0.01-0.77) for pain, and 0.42 (95% CI, 0.16-0.69) and 0.41 (95% CI, 0.08-0.72) for depression. Centralized telecare management coupled with automated symptom monitoring resulted in improved pain and depression outcomes in cancer patients receiving care in geographically dispersed urban and rural oncology practices. clinicaltrials.gov Identifier: NCT00313573.